Nutritional factors modulate the development of both atherosclerosis and autoimmune disease. In recent years, it has been recognized that immunologic injury to artery walls is important in the pathogenesis of atherosclerosis. The kinds of dietary fat, protein, and trace minerals, as well as the amount of calories, have been shown to decrease the severity of immune-complex-induced glomerulonephritis and to prolong survival in mice prone to autoimmune disease. Diets rich in n-3 fatty acids slow the onset of autoimmune disease in NZB/NZW F1 mice, a strain subject to an autoimmune disease resembling systemic lupus erythematosus. A diet containing a high percentage of calories as saturated fat enhances the development of the autoimmune and atherosclerotic vascular lesions in these mice, and diets rich in eicosapentanoic acid prolong their life span. Our objective is to further define the effects of a diet rich in n-3 fatty acids on the development of autoimmune disease and atherosclerosis by studying possible dietary influences on immunologic competence, platelet function, and arterial injury in NZB/NZW F1 mice. Mouse strains not prone to autoimmune disease will be examined for the effect of dietary fat intake on the immune response to foreign protein. Dietary modulation of the immune response to self-antigens will be investigated in vasectomized mice, a model of natural immunization. The effects of a diet rich in n-3 fatty acids on mortality in a mouse strain genetically predisposed to severe degenerative coronary artery disease will also be investigated. This research should provide information on the efficacy of certain dietary regimens in relieving or preventing pathologic sequelae of autoimmune and immune-complex diseases, particularly atherosclerosis and glomerulonphritis.